Psychiatric medications, science, marketing, psychiatry in general, and occasionally clinical psychology. Questioning the role of key opinion leaders and the use of "science" to promote commercial ends rather than the needs of people with mental health concerns.

Thursday, March 01, 2007

Marissa Miller has a fine post about desvenlafaxine (Pristiq), Wyeth's attempt to cover up for their bestseller Effexor coming off patent in the near future. Coverup? Considering that desvenlafaxine is a clear knockoff of Effexor (venlafaxine), yes, I'm sticking with that descriptor.Why do research to develop an innovative medication when you can just sell one that is quite highly similar to the one that is already a sales blockbuster?

The idea is not new – make a drug that very closely resembles your existing product, then get it FDA-approved slightly before the old one goes off patent. Lexapro-Celexa, Invega-Risperdal, and now Effexor-Pristiq.The new drug offers no advantage over the drug that is about to go generic, and why would it – if you have a red 1975 Ford Pinto or a green 1975 Pinto, you still have the same crappy car.

Aren’t patents supposed to protect inventions that possess the potential to benefit people? Aren’t patents supposed to reward creativity?There is no creativity here – we’re talking a slight manipulation of a molecule to create a new compound that is no better than the first one.

But the blame does not just lie with the patent process. Why are physicians prone to fall for this game? Why do so many physicians prescribe Lexapro (escitalopram), which is pert-near a clone of Celexa (citalopram), when Lexapro is much more pricey? In fact according to Walgreens, 90 pills of 10mg generic citalopram will run $127.59, whereas the same supply of Lexapro costs $210.79. The marketing miracle that constitutes the heart and soul of modern psychiatry is damn good at convincing physicians that newer equals better.

Perhaps if physicians received adequate training in research methods and statistics during medical school, they could actually learn to critically review clinical trial data to discover that the ploy of near-clone medicines usually does nothing but increase costs. Then doctors could also laugh their way through continuing medical education or, better yet, insist that CME start to resemble education rather than advertising.

While I definitely agree with your sentiments about CME and the greed/laziness of the pharmas, it is a common misconception that patents are supposed to reward creativity.

Governments award patents simply to encourage (rather than reward) "research and development" by allowing patentees to exploit their invention exclusively for a finite period. In return, the patentee makes a full disclosure of the invention, which becomes available to the public.

Sometimes, there is little point in applying to have an invention patented, regardless of its novelty and usefulness. A pharma considering applying for a patent for a particular drug asks itself the following questions: Is anyone likely to pay for this drug? Is anyone else likely to try and make money out of this drug? If the answer is 'yes' on both counts, an application will be made, strictly based on these commercial considerations.

What a patent provides is a specific kind of protection: the right to stop others from exploiting your invention by appealing to the patent office in the jurisdiction in which the exploitation is taking place. Note that this is not the same as the right (or the means) to exploit the invention yourself. The application process is an expensive one, with costs including official application fees and patent attorneys' fees.

Patents are strictly a commercial tool, and if the pharmas' attorneys can convince the US Patent Office that the new drug is 'novel', then they're well on the way to getting it patented. Either the bar for 'novelty' needs to be raised or (more realistically), as you say, doctors need better training in research methods and statistics, and a bit of consciousness-raising when it comes to the wicked ways of the pharmas. Through your blog, you're doing quite a bit of the latter, which is great.

As always I read your blog, when I can with much interest, but I also bring a different perspective to your forum.

What you seem to lack and understandably so is the clinical aspect of the Psychiatrist, patient and the administering of medications and/or other therapies and the responses and/or side-effects to those therapies.

While again I may be very much in agreement with your assessment of this novelty of slight variations in drug formulations I report to you that I have empirical evidence from long time observations and from patient reporting of varying responses and/or side-effects to branded medications and/or their generics that there are differences in patient responses and/or side-effects to these slight differences.

So while the branded and the generic are basically the same it is not all too uncommon to have a favorable response to one and little or no side-effects when compared to the other.

Once again, you really have not elaborated upon the patient population that you treat but from my many years of battling my spouse’s mood disorder and my knowledge of a large number of other patients afflicted with a similar illness are not unusual to go through the pharmacopeias of medications unsuccessfully and without long-term remission.

Once again I’ll ask you, “What other alternatives would you suggest?” when medications are ineffective and now that the FDA has shot down TMS and CMS has rendered a non-favorable decision toward VNS.

Herb, I'm not sure I understand why someone could have a favourable response to a branded drug and an unfavourable response to its generic equivalent or vice-versa - aren't they the same drug? The question of whether or not this does occur involves both logical and empirical considerations.

The only way I can imagine this happening is if the 'two' drugs are prescribed a significant time apart, during which some kind of epiphany or attitude/emotional state change has taken place - which, in the absence of any intervening pharmaceutical alteration to brain function, really only amounts to the placebo effect. (I'm assuming here that, within the confines of the deeply Cartesian medical model, the term 'placebo effect' must necessarily encompass changes to brain function that are neither physically nor pharmaceutically induced.)

What I can share with you comes from years of personal experiences as well as numerous narratives shared with me as I was a former DBSA (Depression Bipolar Support Alliance) support group facilitator amongst the many hats I've worn is that individuals have responded differently to branded versus generic medications.

Like CL PSYCH analyzing and sharing his knowledge and evaluations and shortcomings of many study programs etc the formal line is that there is supposed to be no difference between branded and generic drugs. I personally do not believe this to be true. Maybe CL PSYCH could better elaborate and answer that question but here’s the formal line:

I'll probably post on Lexapro soon. I've had a terrible experience with it and I'd like others to know about it. I almost ended up taking Celexa not knowing that it was a version of Lexapro. Glad I avoided that.

I'm not sure that physicians necessarily are convinced that "newer equals better."

I think the calculation is more that "newer equals less hassles." There are some ugly, ugly stories about the pressure put on the physician who wanted to go public with Vioxx's problems; obviously a patient is less likely to hear that a drug he or she is on has problems if it has "guardian angels." Which, of course, doesn't mean, that the patient won't experience the problems.

Zyprexa, for example, was promoted as causing less extra-pyramidal symptoms, which, of course, is to be expected if it's an anti-cholinergic, and hence also has the activity otherwise found in the antidotes to such problems. For a while, there was the belief that they did not cause the tardive syndromes.

If a doctor bucks the system, and prescribes, say, an older medication that may indeed be better, if any side-effects pop up, he runs the risk of being held liable for negligence, even if the true cost-benefit ratio, as opposed to the PR-befogged cost-benefit ratio, is strongly in favor of the older preparation.

Do not underestimate the chilling effect of malpractice worries. Doctors may not as much be stupid, as unwilling to sacrifice a kingdom for a horse.

Know matter how many you may have, the plural of anecdote is not data.

Given (a) the rather large placebo effect seen in many of these disorders, (b) the natural regression to the mean phenomena (oft overlooked by most doctors), and (c) the truly subjective nature of these "disorders" especially as it relates to and impacts reporting, it is of little analytical value to constantly refer to "personal experiences" or your observations or stories of others observations.

Here is a suggestion: an experiment between a brand name placebo and generic placebo in depressed and bipolar patients. I bet that you would see a significant difference.

Would that confirm or contradict your personal experiences?

I suspect it would be in agreement with your observations, yet would completely undermine your conclusion.

I know in a recent ruling by CMS one of their concerns was for “empirical evidence.”

As I wrote to CMS I also supplied a definition of “empirical” as I do for you today.

“EmpiricalFunction: adjective1 : originating in or based on observation or experience "empirical data"2 : relying on experience or observation alone often without due regard for system and theory "an empirical basis for the theory"3 : capable of being verified or disproved by observation or experiment "empirical laws”

http://www.m-w.com/cgi-bin/dictionary?book=Dictionary&va=empirical

While I do not dismiss the efficacy of the “placebo effect” I am also keenly aware of the fact that the “placebo effect” does not take into account duration (period of time of the remission). In honor of Drs. Lurie and Wolfe I’ve coined a medical term in their honor which I refer to as “Multi-year Continuous Placebo Effect Phenomenon.”

From my knowledge of a particular treatment option it seems a number of doctors as well as CL PSYCH attribute the favorable response to the “placebo effect” but they cannot cite for me in the medical literature the “placebo effect” as they term it, continuing over several years.

“Here is a suggestion: an experiment between a brand name placebo and generic placebo in depressed and bipolar patients. I bet that you would see a significant difference.” --- nab

I carefully observe and unlike you will leave the theoretical suggestions and experimentation and whatever perceived conclusions up to you.

What is obvious to me, based upon the presentations and commentaries of CL PSYCH and others, I’m more inclined to trust the validity of my observations and the clinical observations of those Psychiatrists that have confirmed my findings and thoughts than all the “data” being put forth by some of these drug studies that are not supposed to be anecdotal.

Herb, it seems that you are more likely to believe your own observations and those from "psychiatrists that have confirmed my findings and thoughts" as opposed to the drug study data. Of course, our observations are one source of data, though I'd prefer to think that scientific studies offer more objective insight than observations of any individual. However, given the biases found in many of the studies that form the so-called evidence base in medicine, then one has to be quite careful about believing the evidence provided by "science."

NAB, your points about the placebo effect, regression to the mean, and the subjective nature of mental disorders are well-taken. These points make our own observations hard to interpret.

Herb also cites some data indicating that generics are not always equivalent to brand name drugs. Keep in mind that some brand name drugs have likewise had problems in manufacturing, where patients weren't getting the dosage they should have been getting. Synthroid was one example, and there have been others. I am not familiar with any evidence that generics or brand name drugs are more prone to these types of problems.

Herb, I may be misinterpreting your argument, but you seem to be saying that for depressed patients who don't respond to a few treatments (a few meds and maybe psychotherapy), then VNS, rTMS, and other treatments should be tried, perhaps out of desperation. All I'm saying is that medicore efficacy data at best does not impress me to the point where I think patients should receive these treatments as a general rule. If they work for some patients, great. But the data are clear that these are not generally treatments upon which one can place a great deal of faith.

“However, given the biases found in many of the studies that form the so-called evidence base in medicine, then one has to be quite careful about believing the evidence provided by "science." --- CL PSYCH

After being enlightened by you and others and from my own “empirical evidence” based upon decades of observations and data keeping “one has to be quite careful about believing the evidence provided by “science.” I’m in full agreement with you and the reason I also continue to disagree with Drs. Laurie and Wolfe and your assessment as it relates to the VNS Therapy for TRD. I’ve also come to learn that “so-called evidence base in medicine” can also be easily corrupted by improper protocols and poorly formulated and/or designed studies.

“I may be misinterpreting your argument, but you seem to be saying that for depressed patients who don't respond to a few treatments (a few meds and maybe psychotherapy), then VNS, rTMS, and other treatments should be tried, perhaps out of desperation.” --- CL PSYCH

Yes to some extent you are misinterpreting my advocacy. How long and how many conventional therapy and treatment options must one patient pursue without efficacy before considering some alternative and/or adjunctive therapy options?

If you are some what familiar with the patient population that I address and speak of and who were the study subjects of the VNS Therapy one learns these individuals, like my spouse, have been seeking some sort of efficacy for decades and have tried considerably more than 10 therapy options with ineffective results. My spouse alone had been attended to by psychologists practicing a minimum of 5 disciplines without even discussing the medications, holistic approaches, ECT etc that were tried on her behalf.

Add to the fact that your commentary further justifies the need for newer and innovative approaches to helping this population of patients. The data presented, valid or not, means little to nothing to me and many of these patients simply because we can relate from personal experience, they do not work regardless of what numbers anyone wants to present. Furthermore, this population of patients would not and is not used in drug studies simply because they’d skew the results.

Whereas you pooh, pooh a statistic of 22% long-term remission rate from the VNS Therapy as seemingly meaningless but I on the other hand and those Psychiatrists attending to this patient population consider that number significant and remarkable in view of the fact nothing else is working.

So maybe the four signatories to the CMS decision (all having no psychiatric credentials) and you have to some time or other step away from your fixation on data and have a fresh look and perspective on what’s really taking place. It might be that the VNS Therapy for TRD is reasonably beneficial for this patient population only all these data mavens have got to take a new perspective and/or rethink and prepare a proper study for a unique medical device application as opposed to another run of the mill drug study.

“If they work for some patients, great.” --- CL PSYCH

You bet your sweat “bippie”, it’s great. If it were for a cancer patient there would be no questions or hesitations but so long as it’s for a patient trying to achieve mental wellness the bigotry, discrimination and stigma will also surface and raise its ugly head; data or no data.

“But the data are clear that these are not generally treatments upon which one can place a great deal of faith.” --- CL PSYCH

Your statement properly applies to all the conventional Psychotherapy options as well as medicinal approaches which have proven ineffective for this patient population and which you tend to illustrate daily in your commentaries. So why not try some new approaches if all else fails?

So again, I’ll throw the ball back into your court. How many ineffective therapies and how many years of this odyssey to obtain mental wellness does this patient population have to endure before you or any of your colleagues or CMS offer up efficacious treatment alternatives?

Good point about liability. Would it matter that a doctor could point to the new med also having severe side effects (though perhaps of a different sort than the older med) or would the PR for the new med quash the doctor's reasoning?

I'm not an MD. What I've heard from those who are, is that if you prescribe the pills de jour that have opinion leaders behind them, malpractice attorneys can't touch you. But once you stray from their recommendations, whatever the facts, you may find yourself at the mercy of a jury; anything that goes wrong happens because you strayed from the approved path. Juries are not always known for being rational, nor are all too many trial lawyers known for their lives of poverty.

Perhaps the key ingredient in most of the new breakthrough products is protection from legal liability.

Generics are tested on about 3 dozen healthy volunteers to check for similar bioavailability, with an allowable range of about 80% to 120% of the brand. It's well-known among psychiatrists that many of these drugs are NOT the same as the brand, especially in conditions in which there is a narrow therapeutic window. I am not a doctor; I am a medical writer and have had panic disorder since I was 17, and I can tell you (n of 1, I know) that generics and brand are NOT the same; that for SOME people, isomers may be much more effective (Lexapro vs Celexa); and that when Prozac first went off patent, psychs knews from patients which generics worked and which didn't (for example, the Par-manufactured generic was the only one my doc would prescribe). The fact that generics are the same as brand drugs is a HUGE lie that all stakeholders--ESPECIALLY insurance companies--would like you to believe. And on the issue of isomers, since we know so little about how these drugs really work (we know they inhibit the reuptake of certain neurotransmitters, but beyond that, we don't know the cascade of events that the brain is performing to maintain homeostasis), the more the merrier. I do agree that "newer is always better" is wrong, but "newer may be the only thing that works for some people to give them a chance at a normal life" is enough for me.

First, there is a difference between a drug and it's isomer. Sometimes a significant difference, and sometimes not. The difference in response to lexapro vs celexa is without a doubt significant. Not only is the response different, but the side effect profile is different as well. As a provider, you couldn't pay me to replace Lexapro with Celexa. They are not the same. Next...generics are not necessarily equivalent to name brand drugs. In some cases they are close enough that it doesn't matter, but in many cases the difference is profound. Anyone that has ever treated thyroid disorders knows absolutely that generic Synthroid IS NOT interchangeable with Synthroid and vice versa. The same goes for oral contraceptives. A woman can do great for years on a name brand pill, and then have nothing but trouble the month after switching to the generic version. This is common, and well known. These pills are not the same, and as quick as I am to jump on big pharma, in this case, you are just plain wrong.

Where's the data that Lexapro is better than Celexa? I don't have the reference on me now, but I recall that the supporting data for this claim is pretty weak. Provide me data that Invega is better than Risperdal, Lexapro better than Celexa, or Pristiq better than Effexor and then I will admit to being "just plain wrong."

While Pristiq is the same active drug as Effexor, I would have to disagree that it is a knockoff. Many drugs have 2 different "shapes" of the same molecule present in equal amounts. When you synthesize the drug, that's the way it forms - the molecules are mirror images of one another. Many times, only one of these molecules is the active drug. Effexor is a mixture of two such molecules. Pristiq contains only the "active" form. (This is a simplification). The result is often a "cleaner" drug - less side effects, better response to therapy. With regards to Pristiq vs. Effexor, within a few hours of missing an Effexor dose, many patients will begin to experience symptoms of discontinuation syndrome - zings, zaps, dizziness. With Pristiq, you have more time - with me, it's about 36 hours. Others may experience other benefits. While I hate being on a patented medication, I prefer taking a cleaner drug with less chemical "garbage." Yes, the drug companies use this to their advantage. But it's not completely meaningless/bogus.

Women must stand up to big pharma’s bullying them to over-medicate with antidepressants washing out their emotions & personalities and interfering being mothers, sisters, brothers, daughters, partners and lovers.. Women are targeted for antidepressants by big Pharma in the same way that tobacco companies targeted us 70 years ago. Drug companies are so effective at selling unhappiness to women that women take more than twice as many antidepressants as men. http://sadnessaddiction.blogspot.com/

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About Me

I'm an academic with a respectable amount of clinical experience and no drug industry funding. Given my lack of time, don't expect multiple daily updates. Certain things about clinical psychology, the drug industry, psychiatry, and academics drive me nuts, and you'll probably pick up on these pet peeves before long...